中国实验血液学杂志最新文献

Objective: To explore the clinical value of plasma von Willebrand factor antigen (VWF:Ag) and VWF activity (VWF:GPIbM) based on ABO blood group in the risk assessment of deep vein thrombosis (DVT).

Methods: A total of 163 patients with DVT who sought medical treatment from March 2021 to December 2022 were selected as the case group, and 135 healthy volunteers during the same period were selected as the control group. The differences of ABO blood groups, plasma VWF:Ag and VWF:GPIbM levels between the two groups were compared. Receiver operating characteristic (ROC) curves were used to evaluate the clinical value of VWF testing in predicting DVT events. Logistic regression analysis was applied to identify risk factors for DVT.

Results: The levels of plasma VWF:Ag and VWF:GPIbM in the DVT group were significantly higher than those in the control group both overall and across ABO blood type subgroups (P < 0.01). Within the DVT group, the levels of plasma VWF:Ag and VWF:GPIbM in patients with non-O blood type were significantly higher than those with blood type O [VWF:Ag: 219.74%±63.64% vs 162.21%±56.03%, P < 0.01; VWF:GPIbM: 228.10% (185.15%, 249.10%) vs 148.25% (116.48%, 225.48%), P < 0.01]. The area under the ROC curve (AUC) of VWF:Ag for predicting DVT events was 0.855, with a cut-off value of 142.4%, sensitivity of 82.2% and specificity of 72.6%; the AUC of VWF:GPIbM was 0.861, with a cut-off value of 141.2%, sensitivity of 84.7%, and specificity of 71.1%. Univariate analysis showed that both VWF:Ag and VWF:GPIbM were influencing factors for DVT events (P < 0.05). Multivariate logistic regression analysis indicated that VWF:Ag>142.4% (OR=13.961, 95%CI : 7.654-25.464, P < 0.01) and VWF:GPIbM>141.2% (OR =17.615, 95%CI : 9.155-33.892, P < 0.01) were independent risk factors for DVT events.

Conclusion: Levels of VWF:Ag and VWF:GPIbM are significantly elevated in non-O blood type DVT patients. VWF:Ag>142.4% and VWF:GPIbM>141.2% are independent risk factors for DVT events. VWF testing based on ABO blood group aids in the precision prevention and control of DVT.

Objective: To explore the efficacy and drug-related toxicity of pediatric patients with recurrent and refractory Langerhans cell histiocytosis(LCH).

Methods: The clinical data of 38 children with refractory and recurrent LCH diagnosed in the Department of Hematology and Oncology of Wuhan Children's Hospital from January 2016 to June 2023 were retrospectively analyzed. The patients received three treatment regimens: regimen A was Cytarabine and Dexamethasone combined with Vindesine, regimen B was Cladribine with Cytarabine, and regimen C was Clofarabine monotherapy. The efficacy and safety of three second-line regimens were evaluated.

Results: Thirty-eight children with refractory and recurrent LCH included 22 males and 16 females, with an age at diagnosis of 2.4(0.4-11.5) years. The median follow-up time was 5.5(1.5-8.5) years. Twenty-one children without risk organ involvement were treated with regimen A, and the 5-year overall survival (OS) rate was 100%, and event-free survival (EFS) rate was (85.7±8.8)%. Among the 17 children with risk organ involvement, 11 cases were treated with regimen B, after 4 courses of treatment, 6 cases achieved no active disease (NAD) and 5 children achieved active disease better (ADB), and 5-year OS rate reached 100%, and 5-year EFS reached 81.8%±11.6%；6 cases were treated with regimen C, and after 6 courses of treatment, 4 cases achieved ADB and 2 cases achieved NAD. Children in group A had hematologic adverse reactions (WHO grade Ⅰ-Ⅲ), all children in group B had hematologic adverse reactions (WHO grade Ⅳ), and three cases had hepatobiliary adverse reactions (WHO grade Ⅱ), and children in group C had hematologic adverse reactions (WHO grade Ⅱ).

Conclusion: The second-line treatment regimens for children with recurrent and refractory LCH based on the involvement of organs at risk has significant efficacy, and further expansion of the sample size and optimization of the treatment regimens are still needed to reduce long-term recurrence rates and toxicity of the treatment.

Objective: To explore the correlation between serum ferritin (SF) levels and the efficacy of platelet transfusion in patients with malignant hematological diseases.

Methods: Patients with malignant hematological diseases who received repeated transfusions of apheresis platelets in Department of Hematology of Aerospace Center Hospital in 2023 were selected. The platelet corrected count increment (CCI) was used to evaluate the efficacy of platelet transfusion. The correlations between sex, age, disease type, transplantation history, red blood cell transfusion history, and SF level and the efficacy of platelet transfusion were analyzed.

Results: A total of 87 patients were included, with a cumulative 326 person-times platelet transfusions. As suggested by one-way analysis of variance, compared with the patients in the age groups of 24-45 years old and 46-66 years old, the patients in the age group of 2-23 years old had a better efficacy of platelet transfusion (P =0.004, P =0.004). There was no significant difference in the efficacy of platelet transfusion between the patients in the age group of 24-45 years old and those in the age group of 46-66 years old (P =0.876). Compared with the patients who had a history of red blood cell transfusion within 3 days, the patients without a history of red blood cell transfusion within 3 days had a better efficacy of platelet transfusion (P < 0.001). Compared with the groups with SF levels of 1.44-2.78 ng/L and >2.78 ng/L, the group with SF levels < 1.44 ng/L had a better efficacy of platelet transfusion (P =0.028, P < 0.001). Compared with the group with SF levels >2.78 ng/L, the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion (P =0.001). After adjusting for age and the history of red blood cell transfusion, the transfusion efficacy of the group with SF levels < 1.44 ng/L was better than that of the groups with SF levels of 1.44-2.78 ng/L and >2.78 ng/L (P =0.021, P < 0.001); Compared with the group with SF levels >2.78 ng/L, the group with SF levels of 1.44-2.78 ng/L had a better efficacy of platelet transfusion (P =0.001). Both univariate and multivariate linear regression models showed that SF levels were negatively correlated with the efficacy of platelet transfusion (P < 0.001).

Conclusion: There is a negative correlation between SF levels and the efficacy of platelet transfusion in patients with malignant hematological diseases. Detection of SF levels may provide guidance for predicting the efficacy of platelet transfusion.

Objective: To explore the expression level of m⁶A methyltransferase ZC3H13 gene in primary acute myeloid leukemia (AML) and its relationship with clinical features and prognosis.

Methods: A total of 131 newly diagnosed AML patients and 12 controls were enrolled from July 1, 2018 to December 1, 2021 in the Hematology Department of the Second Hospital of Shanxi Medical University. RT-qPCR technology was used to detect the expression level of ZC3H13 mRNA in bone marrow (BM) samples. A retrospective analysis was conducted to examine the correlation between ZC3H13 expression level and clinical indicators, gene mutations, and prognosis.

Results: The expression level of ZC3H13 mRNA in primary AML patients was significantly higher than that in the control group ( P <0.001). The white blood cell count, proportion of BM blast cells, and relapse rate in the high ZC3H13 expression group were higher than those in the the low ZC3H13 expression group (all P <0.05), while the Th/Ts ratio was lower ( P <0.01). Univariate survival analysis showed that patients with high expression of ZC3H13 had shorter median overall survival (OS) and disease-free survival (DFS) than those with low expression of ZC3H13 (both P <0.05). The results of multivariate Cox regression analysis showed that high-risk stratification (OS:HR=1.612, 95% CI : 1.151-2.257, P =0.005; DFS:HR=1.551, 95% CI : 1.031-2.335, P =0.035) and high ZC3H13 expression (OS:HR=1.756, 95% CI : 1.028-2.999, P =0.039; DFS:HR=1.935, 95% CI : 1.018-3.678, P =0.044) were both independent risk factors for OS and DFS in AML patients.

Conclusion: The expression of ZC3H13 in AML patients may be related to tumor burden and immune function. Patients with high expression of ZC3H13 have poor prognosis, and high expression of ZC3H13 is an independent risk factor for the prognosis of AML patients.

Objective: To analyze the clinical characteristics and prognosis of children with hematological malignancies complicated by secondary hemophagocytic lymphohistiocytosis (HLH).

Methods: A total of 67 children with HLH admitted to Jinan Second Maternal and Child Health Hospital between June 2020 and June 2024 were selected. Children without hematological malignancies were divided into the non-combined group, and those with hematological malignancies were divided into the combined group. The clinical characteristics and prognosis of the two groups were analyzed.

Results: There were no significant differences in clinical characteristics such as WBC, Hb, PLT between the two groups (P ＞0.05). During the follow-up, the 1- and 2-year overall survival (OS) rates for all children were (88.6±4.1)% and (73.1±7.7)%, respectively. In the non-combined group, 43 children survived and 6 died, with 1- and 2-year OS rates of (95.2±3.3)% and (77.4±9.3)%, respectively. In the combined group, 12 children survived and 6 died, with 1- and 2-year OS rates of (71.8±10.7)% and (62.8±12.6)%, respectively. The OS rate of the combined group was significantly lower than that of the non-combined group (χ²=4.787, P =0.029). The 1- and 2-year event free survival (EFS) rates of the combined group were (61.1±11.5)% and (50.9±13.3)%, respectively.

Conclusion: Children with hematological malignancies complicated by secondary HLH exhibit complex and diverse clinical characteristics. Although favorable short-term therapeutic effects can be achieved, their long-term prognosis tends to be less optimistic.

Objective: To analyze the effect of high serum ferritin (SF) before transplantation on erythrocyte, granulocyte and platelet implantation in unrelated cord blood transplantation (UCBT) patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Methods: The medical records of 60 patients with MDS and AML who underwent UCBT in the First Affiliated Hospital of University of Science and Technology of China from January 2020 to December 2022 were retrospectively collected. According to the SF level before transplantation, they were divided into high SF group (SF≥1 000 μg/L, n=20) and non-high SF group (SF<1 000 μg/L, n=40). The red blood cell (RBC) infusion volume before transplantation, implantation time of RBC, granulocyte and platelet, implantation risk and prognosis were analyzed and compared between the two groups.

Results: There was no correlation between the level of SF before transplantation and RBC infusion. After transplantation, the median implantation time of RBC in the high SF group was 28.5(14-149) d, which was longer than 21(10-83) d in the non-high SF group ( P < 0.05). The median time of granulocyte engraftment in the high SF group was 16.5(12-63) d, while that in the non-high SF group was 16(12-49) d, with no statistical difference between the two groups (P >0.05). The median platelet engraftment time in the high SF group was 45(12-206) d, while that in the non-high SF group was 35.5(14-149) d, with no statistical difference between the two groups (P >0.05). Kaplan-Meier cumulative implantation probability analysis showed that the rate of erythroid implantation in the non-high SF group was higher than that in the high SF group ( P < 0.05), while there was no significant difference in the rates of granulocyte and platelet implantation between the two groups (P >0.05). The 1-year overall survival rates of the non-high SF group and high SF group were 95% and 90%, respectively, with no statistical difference between the two groups (P >0.05).

Conclusion: SF levels before cord blood transplantation in MDS and AML patients have an impact on post transplant erythroid implantation. Detecting and intervening of iron load in patients before transplant may be beneficial for improving implantation and prognosis.

Objective: To investigate the role of platelet-derived zyxin in promoting tumor migration by platelets.

Methods: The gene expression profile of platelets was analyzed from cancer patients by using the GEO database. Isolated platelets from wild-type (WT) and Zyx^-/- mice were co-cultured with B16F10 cells labeled with green fluorescence to investigate the influence of zyxin deficiency on tumor cell migration, invasion, and wound healing. Optical microscopy was employed to evaluate the impact of zyxin deficiency on epithelial-mesenchymal transition (EMT) in B16F10 cells induced by platelets. Employing specific markers to label platelets, fluorescence confocal microscopy was utilized to investigate the impact of platelet-derived zyxin on the binding between tumor cells and platelets. And an aggregometer was employed to observe the influence of zyxin deficiency on tumor cell-induced platelet aggregation.

Results: Compared to platelets from healthy volunteers, zyxin was upregulated in platelets from cancer patients. Zyx^-/- mouse platelets exhibited a significant reduction in tumor cell invasion and migration, impaired wound healing, and delayed tumor cell EMT compared to WT mouse platelets. Additionally, zyxin deficiency attenuated the interaction between platelets and tumor cells, and diminished the capacity for tumor cell-induced platelet aggregation.

Conclusion: Platelet-derived zyxin deficiency diminishes platelet-tumor cell interactions and weakens the ability of tumor cell-induced platelet aggregation, ultimately suppressing tumor cell migration.

Objective: To analyze the genetic characteristics of the VWF gene c. 7332G>A nonsense mutation and explore its molecular pathogenesis.

Methods: Phenotypic diagnosis of the proband was performed using VWF:Ag, VWF:RCo, FⅧ:C and multimeric analysis. The probands were genotyped by NGS whole-exome sequencing, and the sequencing results were validated by sanger sequencing. The family members were genotyped by Sanger sequencing. The VWF gene c. 7332G>A nonsense mutant plasmid was constructed. After transfection, the function of VWF gene c. 7332G>A mutant plasmid was verified at cell level in vitro. The mRNA level was detected by qRT-PCR, and the expression level of protein was detected by Western blot, the function of multimerization was verified by the multimeric analysis.

Results: VWF:Ag and VWF:RCo were all less than 3% in the proband, and the multimeric analysis showed multimer deficiency. The proband was diagnosed as type 3 VWD. The homozygous nonsense mutation of VWF gene c.7332G>A was detected by gene sequencing. The VWF mRNA level of the mutant plasmid was decreased, and the VWF protein expression in the cell supernatant was decreased, the mutant protein was truncated and the function of VWF multimerization was impaired.

Conclusion: A homozygous mutation in exon 43 of VWF gene, c.7332G>A, was responsible for the probands type 3 VWD in the proband. The mutation caused a decrease in the relative level of VWF mRNA and protein, and impaired the function of VWF multimerization.

Objective: Non-targeted metabolomics based on ultra-performance liquid chromatography mass spectrometry (UPLC-MS) platform was used to study the metabolic characteristics of multiple myeloma (MM) patients, and explore potential new metabolic mechanisms affecting the occurrence and development of MM.

Methods: The study enrolled 42 MM patients, including 21 newly diagnosed (ND) patients and 21 relapsed patients (RP), and 21 age-sex matched healthy controls (HC) as subjects. UPLC-MS analysis platform was used to detect small molecule metabolites in serum of the subjects. Principal component analysis (PCA), orthogonal partial least-squared discriminant analysis (OPLS-DA) and 200 random permutations were used to analyze the differences of metabolic profiles among groups. Identification of differential metabolites was completed in the Human Metabolome Database (HMDB) and abnormal metabolic pathway analysis was performed using the KEGG database.

Results: The metabolic profiles of MM patients and healthy controls were significantly separated in both PCA and OPLS-DA models, while the metabolic profiles of newly diagnosed and relapsed MM patients were significantly separated only in OPLS-DA model. In ND vs HC, RP vs HC and RP vs ND cohorts, 19, 24 and 18 differential metabolites were identified respectively, mainly sphingolipids, glycerophospholipids and fatty acyl amino acids. The metabolic pathway abnormalities in newly diagnosed and relapsed MM patients were mainly manifested in sphingolipid metabolism and glycerophospholipid metabolism compared to healthy controls. Compared with newly diagnosed MM patients, relapsed MM patients were mainly manifested in sphingolipid metabolism and ether-lipid metabolism.

Conclusion: The metabolic profiles of MM patients are significantly different from those of healthy people. Relapsed MM patients and newly diagnosed MM patients have similar metabolic profiles, but there are still some differences. Glycerophospholipid metabolism, sphingolipid meta- bolism and ether-lipid metabolism may play important biological roles in the occurrence and development of MM.

Objective: To observe the efficacy and safety of polatuzumab vedotin (pola) combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma (R/R DLBCL).

Methods: A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected. All patients were treated with pola combined with chemotherapy regimens such as BR, R-GDP, R-CHOP, or other regimens.

Results: All 23 patients were evaluable for efficacy, with 10 achieving complete response (CR), 7 partial response (PR), 3 stable disease (SD), and 3 progressive disease (PD). The most common adverse events included myelosuppression, fever, and pulmonary infection. No severe adverse events resulted in drug withdrawal.

Conclusion: Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.